Infusion site leak detection device

ABSTRACT

An infusion set or patch pump is provided for delivering a pharmaceutical agent, such as insulin, to a patient. The infusion set or patch pump has a recessed portion in the bottom face containing a hydrogel and a reactant capable of producing a color change upon contact with the pharmaceutical agent. The reactant includes a mixture of potassium persulfate and 4-aminoantipyrine and optionally horseradish peroxidase, and produces a rapid visually detectable color change when contacted with phenol and/or m-cresol contained in insulin as stabilizing agents.

CROSS REFERENCE TO RELATED APPLICATION

This application is a divisional application of U.S. patent applicationSer. No. 14/045,261, filed Oct. 3, 2013, which claims the benefit ofU.S. Provisional Patent Application No. 61/711,285, filed Oct. 9, 2012,the entire contents of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention is directed to a drug delivery device having aleak detector. The present invention is particularly directed to aninsulin infusion set that exhibits a visual color change in response toleakage at an infusion site.

BACKGROUND OF THE INVENTION

For patients with diabetes, there are two principal modes of dailyinsulin therapy. The first mode includes syringes and insulin pens.These devices are simple to use and are relatively low in cost, but theyrequire a needle stick at each injection, typically three to four timesper day. The second mode includes insulin infusion therapy, whichutilizes an insulin pump. Infusion pumps, although more complex andexpensive than syringes and pens, offer the advantages of continuousinfusion of insulin via an infusion cannula, precision dosing, andprogrammable delivery schedules.

The use of an infusion pump requires the use of a disposable component,typically referred to as an infusion set, line set, extension set orpump set, which conveys the insulin from a reservoir within the pumpinto the skin of the user. An infusion set typically consists of a pumpconnector, a length of tubing, and a hub or base from which an infusioncannula (i.e., an infusion needle or a flexible catheter) extends. Thehub or base has an adhesive which retains the base on the skin surfaceduring use, and which may be applied to the skin manually or with theaid of a manual or automatic insertion device. In most cases, adetachable fluid connector is provided to allow the pump tubing to bedisconnected from the hub or base of the infusion set when the userwishes to shower, bathe or swim.

A second way of providing insulin infusion therapy is by means of apatch pump. A patch pump is a self-contained device incorporating aninsulin reservoir, pump and cannula in a single housing that can beadhered to the user's skin. A patch pump offers the advantage of notrequiring the user to disconnect pump tubing when the user wishes toshower, bathe or swim.

A problem with infusion sets and patch pumps occurs when the cannulaseparates from the skin of the patient or becomes dislodged such thatleakage occurs at the infusion site. Infusion pumps generally dispenseinsulin in small volumes for long periods of time. When leakage occurs,it is often not noticed by the patient for an extended length of time,resulting in an improper dosage.

Accordingly, there is a continuing need in the industry for improvedinfusion sets and patch pumps that provide adequate leak detection tothe patient.

SUMMARY OF THE INVENTION

The present invention is directed to a drug delivery system having aleak detection system. The invention is particularly directed to aninsulin infusion device having a leak detection device for detectingleaks at an infusion site.

Accordingly, one object of the present invention is to provide a fluiddelivery device, an insulin delivery device, an infusion set, patch pumpor other delivery device having a leak detection component for providinga signal to the patient that leakage at the infusion site has occurred.

Another feature of the invention is to provide an insulin deliverydevice such as an infusion set, patch pump or other delivery device thatprovides the patient with a visible indicator that leakage has occurredat an infusion site. The visible indicator in one embodiment is based ona color change of the device, component or material at the infusionsite.

An infusion set or patch pump in an embodiment of the invention includesa cannula for penetrating the skin of a patient for delivering a drug orother pharmaceutical agent. A leak detector is provided around thecannula which undergoes a color change as a result of a chemicalreaction with one or more compounds in the drug or pharmaceutical agentwith a compound on or associated with the leak detector. The leakdetector contains chemical compounds that undergo a rapid color changecompared to the prior devices when in contact with the drug orpharmaceutical agent.

The fluid or insulin delivery device such as an infusion set or patchpump in an embodiment of the present invention has a base with a bottomface for attaching to the skin of the patient. A center portion of thebase has a recessed area and a cannula extending from the base throughthe recessed area so that the recessed area surrounds the infusion sitewhen attached to the patient. A leak detector capable of undergoing achemical change when contacted with a drug or pharmaceutical agent isprovided in the recessed area. In one embodiment, the leak detectorsurrounds the cannula and is spaced from the cannula a distance todefine a cavity for capturing and retaining the drug or pharmaceuticalagent leaking from the infusion site. The infusion set or patch pumpincludes a clear, transparent portion or window to visualize the colorchange occurring in the leak detector at the infusion site.

The leak detector in an embodiment of the invention is a hydrogel havingat least one reactant contained therein capable of reacting with acompound of the drug or pharmaceutical agent to produce a visible colorchange. The hydrogel can be attached to the base of the infusion set orpatch pump around the cannula. In a preferred embodiment, the hydrogelincludes an adhesive layer for attaching the hydrogel in the recessedarea of the infusion set around the cannula.

The chemical compounds of the leak detector are capable of producing acolor change when contacted by one or more compounds contained in thedrug or pharmaceutical, such as a stabilizing agent. In one preferredembodiment, the drug is insulin containing phenolic stabilizing agentssuch as phenol and m-cresol. The reactive compounds in the leak detectorare potassium persulfate and 4-aminoantipyrine, which react with thephenol and m-cresol. Optionally, horseradish peroxidase or other enzymeis added to produce a rapid color change.

The various advantages and features of the invention are attained byproviding a fluid delivery device for introducing a fluid to a patientcomprising a fluid supply containing an active compound and at least onestabilizing compound. A delivery element is adapted for penetrating theskin of the patient and delivering the fluid to the patient. Thedelivery device in one embodiment has a leak detector that includespotassium persulfate and 4-aminoantipyrine in an amount sufficient toproduce a visible color change when in contact with stabilizingcompounds in the fluid.

The features of the invention are further attained in one embodiment byproviding an insulin delivery device comprising an insulin supply sourcecontaining insulin and at least one phenolic stabilizing compound. Aninfusion set is adapted for penetrating the skin of a patient and havingan interface for contacting skin of the patient. The interface regionhas a leak detector that includes potassium persulfate and4-aminoantipyrine in an amount effective to produce a visible colorchange when contacted with the stabilizing compound.

The features of the invention are also attained by providing an insulindelivery device comprising an insulin supply source containing insulinand an infusion set coupled to the supply source and adapted forpenetrating skin of a patient. The infusion set in one embodiment has abase with an interface for attaching to skin of a patient, a cavityformed in the interface, a cannula in the cavity, and a leakage detectorwithin the cavity and surrounding the cannula. The leakage detector hasat least one reactant capable of undergoing a color change upon contactwith at least one compound in the insulin and is visible through thebase.

The additional features of the invention are attained by providing amethod of detecting a leak between an insulin infusion set and a pointof delivery to a patient. The method comprises providing a leak detectorat the point of delivery. The leak detector in one embodiment includes amixture of potassium sulfate and 4-aminoantipyrine in an amountsufficient to produce a color change upon contact with a phenolicpreservative in insulin leaking from the point of delivery.

These and other advantages and salient features of the invention willbecome apparent from the annexed drawings and the following detaileddescription of the invention which disclose various embodiments of thepresent invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The following is a brief description of the drawings, in which:

FIG. 1 is a perspective view of an insulin infusion set in oneembodiment of the invention;

FIG. 2 is an exploded view of the infusion set of FIG. 1 showing thesupply coupling being disconnected;

FIG. 3 is a cross-sectional view of the infusion set showing leakdetector according to an embodiment of the invention;

FIG. 4 is a bottom perspective view of the infusion set showing the leakdetector;

FIG. 5 is a side view of the infusion set in a second embodiment of theinvention; and

FIG. 6 is a cross-sectional view of the infusion set of FIG. 5.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to a drug delivery device having aleak detection system such as a fluid delivery device or an insulindelivery device. The invention is particularly directed to a fluid orinsulin delivery device having a leak detector that provides a visualindication of leakage at the delivery site. The invention is furtherdirected to a fluid delivery device for delivering a fluid containing anactive agent to a patient. The fluid delivery device is typically a drugdelivery device for delivering a drug such as insulin.

The drug delivery device of the present invention is typically aninsulin delivery device such as an insulin infusion set for connectingto an infusion pump as known in the industry. Alternatively, althoughnot shown in the drawings, it may be a self-contained patch pump havingan internal drug reservoir. The drug delivery device in the illustratedembodiment of the invention includes a fluid supply shown as an infusionset 12 connected to an infusion pump 14 by a conduit or supply tube 16.The infusion set is primarily for the delivery of insulin to a patientat a controlled rate and dosage. However, other fluids can also beadministered by infusion to the patient such as HIV drugs, drugs totreat pulmonary hypertension, pain medications, anti-cancer treatments,vitamins, growth hormones, or other substances.

The delivery device of the invention typically includes an infusion setor other cutaneous or subcutaneous delivery member. The delivery devicehas a chamber for capturing fluids leaking at the delivery site andproducing a visible color change. The fluid delivery device forintroducing a fluid to a patient includes a fluid supply for deliveringa fluid containing an active agent and a stabilizing or preservingagent, a delivery element for penetrating the skin and a leak detector.

Referring to FIGS. 1-4 of the drawings, the infusion set 12 has aflexible base 18 and a centrally located hub 20. The base 18 is made ofa sufficiently flexible material to conform to the patient's skin whenattached. The bottom face of the base 18 includes an adhesive 22 forattaching the base to the patient. A protective peel layer 24 isprovided to cover the adhesive 22 during storage and which can beremoved by the patient at the time of use.

The central hub 20 is attached to the base to provide a substantiallyfluid-tight seal therebetween. The central hub 20 has a top face with afluid port 26 for connecting to a detachable fluid coupling 28.Preferably, hub 20 is made from a clear and transparent plasticmaterial. Port 26 has a substantially cylindrical configuration with anoutwardly extending annular flange 30. The annular flange 30 connects toa corresponding recess in the coupling 28 as shown in FIG. 3. An axialpassage 32 sealed near its upper end by a pre-slit resilient septum 33extends through the port 26 and hub 20 for supplying the fluid to thepatient. A blunt plastic cannula 35 within the fluid connector 28penetrates the septum 33 to establish fluid flow to the infusion set 12.

A cannula 34 or other delivery element for penetrating the skin iscoupled to the hub 20 and extends from an interface region on a bottomface 36 of the hub 20 as shown in FIG. 3. The cannula 34 can be a rigidcannula made of stainless steel or a soft flexible cannula as known inthe art. The soft flexible cannula typically includes an insertionneedle (not shown) that is able to penetrate the skin to position theflexible cannula into the skin after which the insertion needle isremoved. Typically, the infusion set will have a flexible cannula and aninsertion needle as known in the art.

The bottom face 36 of the hub 20 as shown in FIG. 3 includes an annularrecess 40 surrounding a cylindrical cannula support hub 52 and thecannula 34 for forming a cavity in the bottom face of the hub 20.Positioned within the recess 40 is a leak indicator 42. As shown inFIGS. 3 and 4, the leak indicator 42 has an annular shape surroundingthe cannula 34 and cannula support 52 to form an open area to capturethe infusion liquid. In the embodiment shown, the leak indicator 42 hasan annular shape to define an annular cavity 44 surrounding the cannula34 within the recess 40. As shown, annular cavity 44 is formed betweenthe inner wall of hub 20 and the outer surface of cannula support hub52. The leak detector is spaced from the cannula a distance to define anopen area to capture the infusion liquid. Preferably, the leak detector42 has a height corresponding to the depth of the recess 40 as shown inFIG. 3. In alternative embodiments, the leak detector 42 can fill theentire recess 40 so that no gap or space is present between the cannula34 and the leak detector 42. In another embodiment, the leak detector 42can include an inwardly extending portion that extends between the outerwall and inner wall of annular recess 40 with the cavity 44 being formedbelow leak detector 42 so that the cavity 44 surrounds the cannula hub52 and the cannula 34. Preferably, the leak detector extends to thebottom face 36 of the hub 20 to contact the skin of the patient aroundthe cannula 34. In this manner, any fluid leaking at the infusion site46 is captured by the leak detector 42. The recess 44 is generallypreferred to alleviate skin tensioning during insertion of the cannula34. In other embodiments, the leak detector 42 occupies only a portionof the cavity 44, can be formed from segments or can be a plurality ofleak detectors that are contiguous or spaced-apart.

The leak indicator in an embodiment of the present invention is anabsorbent material containing a color-changing component that is able toprovide a visual color indicator in the event of leakage at the infusionsite. The leak detector and the color change is visible by the userthrough the transparent portions of the hub 20. As shown in FIG. 3, theinfusion site 46 at the cannula penetration site is typically whereleakage occurs. The leakage can be the result of an improperly insertedcannula or a cannula that has been partially or completely removed as aresult of movement of the infusion set 12. In preferred embodiments ofthe invention, the leak indicator 42 is positioned to provide a rapidvisual indicator to the patient that leakage has occurred, therebyproviding an opportunity to correct the leakage and provide the intendeddosage. The leak detector 42 provides a visual color indicator ofleakage through the delivery device.

Referring to FIG. 3, leakage occurring at the infusion site 46 iscaptured in the cavity 44 and leak detector 42. The fluid beingdelivered to the patient is absorbed by the leak detector 42. The fluidbeing delivered is absorbed by the leak detector which then reacts withcompounds in the leak detector to provide a visual indicator through thedelivery device. In one preferred embodiment, the hub 20 is made of aclear or transparent material so that the color change in the leakdetector can be viewed by the patient through the top and/or sides ofthe hub 20. In further embodiments of the invention, the fluid coupling28 can also be clear or transparent so that color change can be observedby the patient.

In a preferred embodiment of the invention, the leak detector 42 is madefrom a transparent high diffusion hydrogel having at least one compounddispersed therein that is capable of undergoing a color change whencontacted with the infusion liquid. The hydrogel is preferably formed asa film or cylindrical shaped member having an adhesive backing on oneside for attaching the hydrogel to one or more surfaces of a recess inthe bottom of an infusion set. Examples of hydrogels includepolyacrylamides, silicone hydrogels, crosslinked polyethylene oxide andcrosslinked polyvinylpyrrolidone. The clear or transparent components ofthe infusion set enable visualization of the reaction by a color changethrough one or more parts of the infusion set.

In one embodiment of the invention, the leak indicator is formed withina portion of the hub 20 that has a cylindrical shape. In the embodimentshown in FIGS. 5 and 6, the leak detector 40 is provided within thecylindrical portion 50 of the port 26. The leak detector 40 is visiblethrough the side wall of the cylindrical portion 50 of the port 26 aswell as the top face of the hub 20 to enhance visualization when a colorchange occurs. In the embodiment of FIGS. 5 and 6, the leak detector 42has a cylindrical shape to extend from the bottom face of the hubupwardly along the cylindrical portion 50. The cannula 34 is connectedto the port 26 as shown.

In one embodiment of the invention, the infusion liquid is an insulinformulation. The leak detector contains at least one component thatreacts with a component or compound of the insulin formulation that isnot present in body fluids to avoid giving a false indication of leakageof the insulin formulation. Insulin formulations typically includeinsulin, hexamer zinc stabilizer preservatives, pH buffers, surfactantssuch as glycerol and tonicity agents such as NaCl. Common insulinpreservatives or stabilizing agents include m-cresol, phenol, andmixtures thereof.

In one preferred embodiment of the invention, the leak detector 42includes one or more compounds that react with the stabilizing agents,namely m-cresol and/or phenol, to produce a visual color change when theinfusion liquid is absorbed by the leak detector. The color changingcompounds in the leak detector are preferably clear or opaque initiallyand produce a color change when reacted with the stabilizing agents ofthe insulin or other infusion liquid.

The color changing compounds of an embodiment of the invention include amixture of 4-aminoantipyrine and an oxidizing agent in an effectiveamount to produce a color change by reacting with the stabilizing agentswhen the infusion liquid contacts the leak detector 42. The preferredoxidizing agent is potassium persulfate, K₂S₂O₈. The mixture of4-aminoantipyrine and potassium persulfate reacts with the m-cresoland/or phenol in the insulin formulation to transform the leak detectorfrom a clear hydrogel to a dark blue color that is visible through thetransparent hub 20. Potassium persulfate is a preferred oxidizing agentand has been found to provide a rapid color change in the presence ofphenol, m-cresol and 4-aminoantipyrine compared to other oxidizingagents. For example, it has been found that potassium persulfateprovides a faster color change compared to potassium ferricyanide. Them-cresol and/or phenol react with potassium persulfate and4-aminoantipyrine to produce quinoneimine having a dark blue color thatis visible through the hub 20.

In further embodiments, the hydrogel can also include a catalyst orenzyme to enhance the speed of the reaction and amplify the colorchange. In one embodiment, horseradish peroxidase (HRP) is included inthe hydrogel matrix in combination with the 4-aminoantipyrine andpotassium persulfate. A deep blue complex is formed during the reactionwith m-cresol and phenol. Horseradish peroxidase functions as a catalystto create an enzymatic amplification of the reaction and the bluecomplex formed by the reaction. The presence of the horseradishperoxidase enables rapid detection of small amounts of insulin to enablepatients to observe the leakage reliably and quickly after the leakagestarts.

The amount of the various compounds and components are preferablypresent in an amount effective to provide a prompt and reliable reactiontime for the detection of the leakage of insulin from an infusion site.The pH of the hydrogel is also adjusted to maximize the reaction. Thehydrogel can also contain a contrasting color from the blue reactionproduct to enhance the visualization of the color change. For example,the hydrogel can have a white or cream colored pigment that will enhancethe color change.

While various embodiments have been selected to illustrate theinvention, it will be understood that various changes and modificationscan be made without departing from the scope of the invention as definedin the appended claims and their equivalents.

What is claimed is:
 1. A method of delivering a fluid to a patient by afluid delivery device and detecting leakage from an injection site inthe patient, said method comprising; providing a delivery device havinga base with a bottom face having an adhesive, a hub having a bottomface, a cavity formed in said hub and recessed with respect to saidbottom face of said hub, a cannula configured for being inserted intothe skin of the patient and oriented within said cavity of said hub, anda fluid supply connected to said hub for delivering the fluid containingan active agent and at least one stabilizing agent, and a leak detectorpositioned in said cavity of said hub and surrounding said cannula andspaced inwardly from said adhesive, said leak detector comprisingpotassium persulfate and 4-aminoantipyrine; introducing said catheterinto the injection side on the skin of the patient and attaching saidbase to the skin of the patient by the adhesive; introducing said fluidthrough said cannula into the patient at the injection site andcapturing fluid leakage from said injection site in said cavity wheresaid stabilizing agent in said fluid from said injection site reactswith said leak detector to produce a visible color change that isvisible through said hub when leakage occurs.
 2. The method of claim 1,wherein said leak detector comprises a hydrogel impregnated with saidpotassium persulfate and 4-aminoantipyrine.
 3. The method of claim 2,wherein said hydrogel is attached to said hub by an adhesive surroundingsaid catheter.
 4. The method of claim 1, wherein said catheter is asoft, flexible catheter, and said method comprising introducing saidsoft, flexible catheter into said patient by an introducer needle. 5.The method of claim 4, wherein said hydrogel surrounds said cannula andis spaced inwardly from said cannula.
 6. The method of claim 1, whereinsaid hub of said delivery device has a top face with at least onesubstantially transparent portion to visualize the color change throughsaid at least one substantially transparent portion.
 7. The method ofclaim 1, wherein said active agent comprises insulin and said at leastone stabilizing agent is selected from the group consisting of m-cresol,phenol, and mixtures thereof.
 8. The method of claim 2, wherein saidhydrogel further comprises an effective amount of horseradish peroxidaseto catalyze the reaction.
 9. A method of delivering insulin to aninjection site of a patient and detecting leakage from said injectionsite, said method comprising; providing a delivery device having aninsulin supply source for delivering a fluid containing insulin and atleast one phenolic stabilizing agent to the patient, and an infusion sethaving an interface having a cavity and a contact area for contactingskin of the patient and surrounding said cavity, a cannula in saidcavity, said cavity surrounding said cannula, a leak detector positionedin the cavity and surrounding the cannula, said leak detector includingpotassium persulfate and 4-amino-antipyrine in an amount effective toproduce a visible color change when contacted with the stabilizing agentof said insulin; introducing said catheter into the injection site inthe skin of the patient and attaching said base to said skin of thepatient by the adhesive to surround said injection site and cannula; andintroducing said insulin through said cannula into the patient at theinjection site and capturing insulin leakage from said injection site insaid cavity where said phenolic stabilizing agent leaking from saidinjection site contacts said leak detector in said hub to produce avisible color change that is visible through said hub when leakageoccurs.
 10. The method of claim 9, wherein said at least one stabilizingagent is selected from the group consisting of m-cresol, phenol, andmixtures thereof.
 11. The method of claim 9, wherein said leak detectorfurther comprises an effective amount of horseradish peroxidase tocatalyze the reaction between the potassium persulfate,4-aminoantipyrine and the stabilizing agent.
 12. The method of claim 9,wherein said interface has a hub with a bottom face and said cavity isformed in said hub to surround said cannula to capture insulin leakagein said hub from said cannula at an infusion site.
 13. The method ofclaim 12, wherein said leak detector is positioned in said cavity ofsaid hub around said cannula.
 14. The method of claim 13, wherein saidleak detector further includes a hydrogel containing said potassiumsulfate and 4-aminoantipyrine.
 15. The method of claim 14, wherein saidhydrogel is attached to said interface by an adhesive.
 16. The method ofclaim 14, wherein said interface includes a contact area surroundingsaid cavity, said contact area having an adhesive, and said methodcomprising attaching said contact area to the skin of the patient bysaid adhesive and contain said insulin leakage within said cavity. 16.The method of claim 15, wherein said leak detector is spaced inwardlyfrom said adhesive and spaced outwardly from said cannula.
 18. Themethod of claim 9, wherein said cannula is a soft flexible cannula, andwhere said soft flexible cannula is introduced into the patient by aninsertion needle.
 19. A method of detecting a leak between an insulininfusion set and an injection site of a patient, said method comprising:providing the infusion set having an interface with a base for attachingdirectly to skin of a patient, a cavity formed in the base, and acannula positioned in said cavity and extending from said base adistance to penetrate the skin of the patient, a leak detectorpositioned in said cavity and surrounding said cannula and spacedoutwardly from said cannula a distance to define the cavity, said leakdetector including a mixture of potassium sulfate and 4-aminoantipyride,and said base having a bottom face with an adhesive for attaching to theskin of the patient and surrounding said cavity, leak detector andcannula; attaching said base to the skin and inserting the cannula intothe skin of the patient, introducing insulin through said cannula intosaid patient at said injection site, and capturing insulin leakage insaid cavity at the injection site where said insulin contacts said leakdetector to produce a color change that is visible through saidinterface.
 20. The method of claim 19, wherein said leak detectorfurther comprises horseradish peroxidase.